Direct Cooperation Between Androgen Receptor and E2F1 Reveals a Common Regulation Mechanism for Androgen-Responsive Genes in Prostate Cells
Direct Cooperation Between Androgen Receptor and E2F1 Reveals a Common Regulation Mechanism for Androgen-Responsive Genes in Prostate Cells
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DOI：
10.1210/me.2012-1016
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发表时间：
2012-09-01
影响因子：
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通讯作者：
Samarut, Jacques
中科院分区：
文献类型：
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作者：
Altintas, D. M.;Shukla, M. S.;Samarut, Jacques
我们研究了前列腺细胞中雄激素对 ATAD2 基因表达的调节。 ATAD2 是雄激素受体 (AR) 和 MYC 蛋白的共激活剂。我们发现 ATAD2 表达由 AR 通过位于其调节区远端增强子的 AR 结合序列 (ARBS) 直接调节。该基因还受到 E2F1 转录因子的调节。使用敲低和染色质免疫沉淀技术方法，我们可以证明 AR 和 E2F1 在功能上相互协作并在物理上相互作用。通过对染色质构象的分析，我们得出结论，这种合作是由于 ARBS 和 E2F1 结合位点之间的 ATAD2 启动子区域上的染色质以雄激素依赖性方式循环所致。此外，我们还可以证明，在前列腺癌中过度表达并可能参与肿瘤发展的多个方面的几个基因在其调节区域中具有 ARBS 和 E2F1 结合位点，并且表现出与 ATAD2 相同的两种转录因子的调节机制。 （分子内分泌学26：1531-1541，2012）
We have studied the regulation of ATAD2 gene expression by androgens in prostate cells. ATAD2 is a coactivator of the androgen receptor (AR) and the MYC protein. We showed that ATAD2 expression is directly regulated by AR via an AR binding sequence (ARBS) located in the distal enhancer of its regulatory region. The gene is also regulated by the E2F1 transcription factor. Using knockdown and chromatin immunoprecipitation technique approaches, we could demonstrate that AR and E2F1 functionally collaborate and physically interact between each other. From the analysis of chromatin conformation, we conclude that this cooperation results from a chromatin looping over the ATAD2 promoter region between the ARBS and E2F1 binding site in an androgen-dependent manner. Furthermore, we could show that several genes overexpressed in prostate cancer and potentially involved in several aspects of tumor development have an ARBS and an E2F1 binding site in their regulatory regions and exhibit the same mechanism of regulation by both transcription factors as ATAD2. (Molecular Endocrinology 26: 1531-1541, 2012)